A Large Multicenter Correlation Study of Thyroid Nodule Cytopathology and Histopathology

Department of Medical and Clinical Affairs, Veracyte, Inc., South San Francisco, California 94080, USA.
Thyroid: official journal of the American Thyroid Association (Impact Factor: 4.49). 12/2010; 21(3):243-51. DOI: 10.1089/thy.2010.0243
Source: PubMed


Fine-needle aspiration (FNA) biopsies are the cornerstone of preoperative evaluation of thyroid nodules, but FNA diagnostic performance has varied across different studies. In the course of collecting thyroid FNA specimens for the development of a molecular diagnostic test, local cytology and both local and expert panel surgical pathology results were reviewed.
Prospective FNAs were collected at 21 clinical sites. Banked FNAs were collected from two academic centers. Cytology and corresponding local and expert panel surgical pathology results were compared to each other and to a meta-review of 11 recently published U.S.-based thyroid FNA studies.
FNA diagnostic performance was comparable between the study specimens and the meta-review. Histopathology malignancy rates for prospective clinic FNAs were 34% for cytology indeterminate cases and 98% for cytology malignant cases, comparable to the figures found in the meta-review (34% and 97%, respectively). However, histopathology malignancy rates were higher for cytology benign cases in the prospective clinic FNA subcohort (11%) than in the meta-review (6%, with meta-review rates of 10% at community sites and 2% at academic centers, p < 0.0001). Resection rates for prospective clinic FNAs were also comparable to the meta-review for both cytology indeterminate cases (62% vs. 59%, respectively) and cytology malignant cases (82% vs. 81%, respectively). Surgical pathology categorical disagreement (benign vs. malignant diagnosis) was higher between local pathology and a consensus of the two expert panelists (11%) than between the two expert panelists both pre- (8%) and postconferral (3%).
Although recent guidelines for FNA biopsy and interpretation have been published, the rates of false-positive and false-negative results remain a challenge. Two-thirds of cytology indeterminate cases were benign postoperatively and may decrease with the development of an accurate molecular diagnostic test. High disagreement rates between local and expert panel histopathology diagnosis suggests that central review for surgical diagnoses should be used when developing diagnostic tests based on resected thyroid specimens.

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    • "Application of a panel of mutation analyses including BRAF, RAS, RET/PTC and PAX8/PPAR to nodules with atypical/suspicious cytology classification is reported to have variable sensitivities ranging from 38 to 85%, but high specificities of over 95% for malignancy; this has led some experts to recommend bilateral surgery if a mutation is detected [98]. Recently, a molecular classifier using mRNA expression analysis reported a 96% negative predictive value for cancer in nodule with a diagnosis of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) or follicular/oncocytic follicular neoplasm, with the potential to avoid surgery in those patients with negative test results [97] [99] [100]. Therefore, many laboratories are using 'reflex' molecular testing of thyroid FNA specimens diagnosed as atypical, neoplasm/suspicious for neoplasm and suspicious for papillary carcinoma. "
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    ABSTRACT: Thyroid nodules are common and, depending on the detection technique used, can affect 50% or greater of the population. The primary diagnostic test to assess the nature of these nodules is fine-needle aspiration cytology. Most thyroid nodules are benign and often are multiple. However, the morphology of these nodules may mimic neoplasms showing features such as papillary growth, micro follicles and even oncocytic metaplasia. Lesions with these features may be considered in-determinant, and often require surgical excision to define their nature. The role of cytopathology in this area is to screen those definitely benign nodules, thus preventing surgery and reassuring both the patient and the clinician. In this review, we demonstrate many of the morphological manifestations of nodular goiter and stress the necessity of careful preparatory techniques. Although the past several years have witnessed the development of molecular testing to refine diagnostic cytology in the thyroid, it is still the role of the cytopathologist to identify those "indeterminant" nodules which should be tested. Thus, the cytopathologist contributes both an essential diagnostic and an important cost saving role which hopefully will continue in the future.
    Best Practice & Research: Clinical Endocrinology & Metabolism 08/2014; 28(4). DOI:10.1016/j.beem.2014.01.010 · 4.60 Impact Factor
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    • "In some cases—despite observation of these rules—surgical or clinical follow-up reveals thyroid cancer in patients with cytological diagnosis of benign lesion [2]. Thus, it is justified to perform studies on the usefulness of performing repeat FNA of cytologically diagnosed benign lesions. "
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    ABSTRACT: Purpose. The aim of the study was to compare the risk of thyroid malignancy and efficacy of repeat FNA in patients with thyroid nodules diagnosed cytologically as benign lesion (BL) with features of chronic thyroiditis (BL-CT) and BL without CT features (BL-nCT). Methods. The analysis included 917 patients with BL-CT and 7046 with BL-nCT in the first FNA. Repeat biopsy was carried out in 787 patients of BL-CT and 5147 of BL-nCT; 218 patients of BL-CT and 2462 of BL-nCT were operated; in 88 cases of BL-CT and 563 of BL-nCT both ways of follow-up were available. Results. Outcome of repeat cytology implied surgery more frequently in patients with BL-CT than with BL-nCT-3.2% versus 1.9%, P < 0.05. Incidence of cancer (including incidentalomas) was higher in patients with BL-CT operated after one benign cytology than in patients with two benign FNA outcomes: 10.8% versus 1.6%, P < 0.05. In patients with BL-nCT that difference was not significant: 3.2% versus 2.6%. Conclusions. Patients with thyroid nodules diagnosed as BL with CT features have higher risk of malignancy than patients with BL without CT features. Repeat biopsy significantly lowers percentage of FN results in patients with BL-CT in the first FNA.
    International Journal of Endocrinology 04/2014; 2014(1):967381. DOI:10.1155/2014/967381 · 1.95 Impact Factor
    • "The major reason for the wide range of sensitivity and specificity ratios is the differences in the categorization of “FN/SFN,” “suspicious for malignancy” and “AUS/FLUS” diagnoses. In addition, some authors categorize follicular lesions as histopathologically benign, while others categorize these lesions as malignant.[891718] In our study, we evaluated the follicular lesions in the same category. "
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    ABSTRACT: Background:Fine-needle aspiration cytology (FNAC) in the diagnosis of thyroid nodules is an easy and cost-effective method. The increase in malignancy rates of the excised nodules due to the high sensitivity and specificity rates of the FNAC is remarkable.Aim:The aim of this study was to assess the effectiveness of FNAC in the evaluation of thyroid nodules by comparing the results with histopathologic evaluation and comparing the consistency of the results with the literature.Materials and Methods:In this study, 1607 FNACs of 1333 patients which were classified according to the Bethesda system and 126 histopathological evaluations obtained from this group were evaluated. The mean age of the patients was 51.24 (range: 17-89, 17% male and 83% female). The sensitivity, specificity, positive and negative predictive values, and accuracy rates were evaluated.Results:The sensitivity was 87.1% and specificity was 64.6%. The positive and negative predictive value and accuracy rates were 76.1%, 79.5%, and 77.3%, respectively.Conclusions:In our study, the evaluation of thyroid FNAC samples with Bethesda system highly correlated with the results of histopathological diagnosis. However, combination of additional and advanced diagnostic methods such as immunocytochemical studies and molecular pathology techniques enhance the prognostic value of FNAC in patients with atypia of undetermined significance or follicular lesion of undetermined significance, lesions suspicious for malignancy, and suspected follicular neoplasm.
    Journal of Cytology 04/2014; 31(2):73-8. DOI:10.4103/0970-9371.138666 · 0.37 Impact Factor
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